Method, apparatus and systems for monitoring co2

ABSTRACT

There is provided herein methods, apparatus and systems for evaluating carbon dioxide (CO 2 ) concentration in a subject&#39;s breath, for example in subjects ventilated with High Frequency Ventilation (HFV), the method includes inserting to a trachea of a subject an endotrachial tube (ETT), sampling breath from an area in the trachea located in proximity to a distal end of the endotrachial tube (ETT) and evaluating one or more CO 2  related parameters of the sampled breath.

FIELD OF THE INVENTION

The invention generally relates to method and apparatus for monitoringcarbon dioxide (CO₂) in breath.

BACKGROUND

Continuous noninvasive monitoring of carbon dioxide (CO₂) levels ininfants, particularly in a Neonatal Intensive Care Unit (NICU), isconsidered very important mainly in order to protect subjects such asinfants from the complications of hypocarbia (less than the normal levelof carbon dioxide in the blood) and hypercarbia (more than the normallevel of carbon dioxide in the blood) and to avoid extra blood samplingwhich may cause anemia, discomfort, and pain. Noninvasive monitoring ofcarbon dioxide (CO₂) levels typically refers to exhaled breath analysisalso referred to as capnography.

Capnography is a common method of monitoring and optionally displayingthe CO₂ level(s), CO₂ waveform(s) and/or other CO₂ related parameters,such as End Tidal CO₂ (EtCO₂), in exhaled breath. Capnography alsoprovides information relating to cell metabolism, blood per fusion,alveolar ventilation and other body functions or conditions, and mayenable real-time diagnosis of patho-physiological abnormalities as wellas technical problems related to ventilation. In intubated subjects(such as patients) capnography is performed by sampling exhaled breatharound the exit of the endotrachial tube (ETT) at a sampling regionbetween the proximal end of the ETT (close to the subject's mouth) andthe ventilator circuit. In intubated small children and infants,however, capnography is not commonly used since it does not consistentlyprovide satisfactory results. One of the reasons for the lack ofsatisfactory results in small children, infants and/or neonatesespecially neonates, relates to the use of uncuffed endotrachial tubes(ETTs) during their ventilation. A cuff is an inflatable balloon on theouter surface of the ETT used to hold the ETT in place and to close offthe ventilated air exiting the ETT at its distal end (towards thesubject's lung) from escaping around the tube outwards. In case of smallchildren and/or infants, and especially neonates, cuffed ETTs aregenerally not used due to the risk of perforating or otherwise harmingthe gentle membrane of their trachea. The use of uncuffed ETTs resultsin ventilated air escaping around the tube during inhalation. Althoughthis can be compensated for by changing the ventilator parameters, agreater problem arises during breath sampling (both in mainstream andside-stream capnography) which depends on the exhaled breath returningback through the ETT towards the sampling region. The uncuffed ETTallows the exhaled breath to return between the ETT and trachea, and outthrough the mouth without returning back through the ETT towards thesampling region. This is further exaggerated, since with neonates theETT internal diameter is very small, typically between 2.5 to 4 mm,which imposes a large restriction, enhancing further the possibility ofexhaled breath escaping round the tube. The small volume of exhaledbreath (which is only a Traction of the low tidal volumes of infants andneonates) that does manage to return back through the ETT is alsodiluted with clean ventilated air (often present in a “dead space” ofthe ETT) which leads to difficult breath sampling and erroneous CO₂readings.

This problem is further enhanced in mainstream capnography, in which therequired airway section is connected inline between the proximal end ofthe ETT (close to the subject's mouth) and the ventilator circuit. Thus,it adds more dead space, competes for tidal volume, and may also cause akink in the ETT, especially in small premature infants. When a flowsensor is connected to the ETT, the use of mainstream capnography iseven more cumbersome.

There is thus a need in the art for methods, systems and apparatusesthat would allow accurate CO₂ monitoring, particularly in smallchildren, infants or neonates.

High Frequency Ventilation (HFV)

In addition to the problems discussed hereinabove, which relates to CO₂monitoring, the ventilation itself particularly in neonates, but alsowith children and adults, still suffers from significant difficulties.Some neonates cannot be adequately ventilated even with sophisticatedconventional ventilation. Therefore respiratory insufficiency remainsone of the major causes of neonatal mortality. Intensification ofconventional ventilation with higher rates and airway pressures leads toan increased incidence of barotrauma.

Especially, the high shearing forces resulting from large pressureamplitudes damage the lung tissue. High Frequency Ventilators (HFV) beenshown to resolve or at least ameliorate this issue in many cases.

High Frequency Ventilation (HFV) is a technique of ventilation that usesrespiratory rates that greatly exceed the rate of normal breathing.There are three main types of HFV:

-   -   1) High frequency positive pressure ventilation (HPPV, rate        60-150 breaths/minute);    -   2) High frequency jet ventilation (HFJV, rate 100-600        breaths/minute); and    -   3) High frequency oscillatory ventilation (HFOV, rate 300-3000        breaths/minute).

During conventional ventilation direct alveolar ventilation accomplishespulmonary gas exchange. According to the classic concept of pulmonaryventilation an amount of gas reaching the alveoli equals the appliedtidal volume minus the dead space volume. At tidal volumes below thesize of the anatomical dead space this model fails to explain gasexchange. Instead, considerable mixing of fresh and exhaled gas in theairways and lungs is believed to be the key to the success of HFV inventilating the lung at such very low tidal volumes. Among theadvantages of high frequency oscillatory ventilation as compared toeither conventional positive pressure or jet ventilation is its abilityto promote gas exchange while using tidal volumes that are less thandead space. The ability of HFV to maintain oxygenation and ventilationwhile using minimal tidal volumes allows minimization of barotrauma andthus reduces the morbidity associated with ventilation.

Currently, two of the most important values that determine therespiratory therapy, such as HFV, is the Blood Gas CO₂ (PaCO₂) and theSpO₂ (the amount of oxygen being carried by the red blood cell in theblood). In order to monitor the subject's gas concentration in theblood, however, a blood sample must be taken. Blood sampling involvespain, discomfort and risk of infection. Especially with neonates, sincethe volume of blood is very small, each blood test takes a measurablepercentage of the neonate's blood. This dictates periodic bloodtransfusions, where each blood transfusion promotes a further danger tothe neonate or other subject.

There is thus a need in the art for methods, systems and apparatusesthat would permit and facilitate accurate measurement(s) of medicalparameter(s) for the evaluation and control of HFV therapy in subjects,particularly, but not only, in small children, infants or neonates.

SUMMARY

This summary section should not be construed as limiting the inventionto any features described in this summary section.

General Sampling in Neonatal Environment

Some embodiments of the invention are generally directed to a method andapparatus for monitoring breath carbon dioxide (CO₂) in subjects,particularly, but not limited to, small children and infants, from aposition much closer to the bronchial tubes than the current samplingposition. This type of CO₂ sampling and evaluation may also be referredto as a “distal CO₂ measurement”.

As discussed hereinabove, the current sampling configuration isproblematic since it involves sampling from an area close to subject'smouth and to the proximal end of the ETT, wherein CO₂ is mixed withventilated air, which eventually leads to erroneous CO₂ readings. Thisis particularly problematic when using an uncuffed endotrachial tube(ETT), which is very common in small children, infants and neonates. Itwas found that sampling breath from a position at a lower section of thetrachea closer to the bronchial tubes (distal CO₂ measurement) may beless susceptible to air leak and/or mixing of the measured CO₂ withinhaled air. More particularly, sampling breath for distal CO₂measurement may be performed at the distal end of the ETT which isadapted to be positioned inside the bronchial tube. According to someembodiments, sampling breath for distal CO₂ measurement may be performedby inserting a catheter into the ETT, wherein the catheter is adapted tosample CO₂. According to some embodiments, sampling breath for distalCO₂ measurement may be performed by sampling breath through the second(extra) lumen (typically having very small diameter compared to the mainlumen) of a double lumen ETT.

Sampling in Subjects Treated with High Frequency Ventilation (HFV)

Additional or alternative embodiments of the invention are generallydirected to a method and apparatus for using capnography in monitoringbreath carbon dioxide (CO₂) in subjects, particularly, but not limbedto, small children and infants, who are ventilated by High FrequencyVentilation (HFV) technique.

When considering capnography for replacing at least some of the bloodgas samples, and in general to provide continuous monitoring for HFV(such as HFOV) mode of ventilation, some difficulties arise:

-   -   a) Capnographs are generally designed to detect breath cycles up        to rates of about 120-150 breaths per minute. As mentioned        above, with HFV, frequencies are much higher. A limiting factor        being the response time, which even for the fastest capnograph        systems is generally more than 100 msec, which is far too slow        for this mode of ventilation. In addition, it is most probable,        that even if one had a capnograph system that was faster and        able to detect changes at frequencies similar to those of the        HFV ventilation mode, no breath cycle would be seen Since the        CO₂ is mainly diffusing out, and only ripples would be seen        caused by the pressure fluctuations.    -   b) Capnographs are generally designed such that if a breath        cycle (a minimal sinusoidal wave) is not detected, a “no breath”        alarm is triggered.    -   c) More important, as mentioned herein the considerable mixing        of fresh and exhaled gas in the airways and lungs creates a        status where the CO₂ concentration along the subject's airway        changes and decreases so that at the standard position for        capnography sampling, either mainstream or sidestream, the        concentration will be much lower than what is really occurring        in the lungs. Hence, CO₂ as currently measured would not be        comparative to the blood gas value, and even if it had some        correlation, it would have very low resolution. It was found        that the CO₂ concentrations at these standard portions to be        about eight times lower than those measured for standard        ventilation modes. It is also noted that since there is no        breath cycle, the CO₂ concentration is also an average value        without peaks.

According to some embodiments of the invention, there are provided amethod and apparatus that may overcome one or more issues related todifficulties such as those discussed hereinabove, and to facilitate CO₂sampling and monitoring in subjects (for example, but not limited to,children, infants, and neonates) ventilated by the HFV mode. Accordingto some embodiments of the invention, there are provided a method andapparatus for CO₂ sampling and monitoring in subjects (but not limitedto, children, infants, and neonates) ventilated by the HFV mode.

According to some embodiments of the invention, there is provided amethod for evaluating concentration of carbon dioxide (CO₂) in asubject's breath, the method includes inserting an endotrachial tube(ETT) to a subject in a need thereof, sampling breath from an area inthe trachea located its proximity to a distal end of the endotrachialtube (ETT) and evaluating one or more parameters related toconcentration of CO₂ in the sampled breath.

According to some embodiments, sampling breath may include inserting asecond tube into the endotrachial tube (ETT), such that the second tubereaches the area located in proximity to the distal end of theendotrachial tube (ETT), and sampling the breath through the secondtube.

The endotrachial tube (ETT) may be a double lumen endotrachial tube(ETT) having a main endotrachial tube and a second endotrachial tube,wherein sampling of breath is conducted through the second endotrachialtube. The second endotrachial tube may located essentially inside thelumen of the main endotrachial tube, essentially inside the wall of themain endotrachial tube or partly in both. The second endotrachial tubeis located outside the main endotrachial tube. The second endotrachialtube may have a diameter smaller than the diameter of the mainendotrachial tube.

According to some embodiments, sampling may further induce connecting asampling line to a connector located a proximal end of the secondendotrachial tube.

According to some embodiments, the method may further include performingsuction of fluid from the second endotrachial tube, wherein when suctionis performed sampling is temporarily stopped and when sampling isperformed suction is stopped.

According to some embodiments, the method may be used in children,infants and/or neonates.

According to some embodiments, the method may be used in subjectsventilated with High Frequency Ventilation (HFV), such as, but notlimited to, children, infants and/or neonates.

According to some embodiments of the invention, there is provided adouble lumen endotrachial tube (ETT) adapted for sampling breath from asubject for the evaluation of one or more parameters related toconcentration of carbon dioxide (CO₂) in the sampled breath, the doublelumen endotrachial tube (ETT) includes a main endotrachial tube and asecond endotrachial tube, the second endotrachial tube is adapted tosample breath from a distal position in a trachea of a subject. Thedistal position in a trachea of a subject may include an area of thetrachea located in proximity to a distal end of the endotrachial tube(ETT). The distal position in a trachea of a subject may include an areaof the trachea located in proximity to a distal end of the secondendotrachial tube.

According to some embodiments of the invention, there is provided abreath sampling system including a double lumen endotrachial tube (ETT)adapted for sampling breath from a subject for the evaluation of one ormore parameters related to concentration of carbon dioxide (CO₂) in thesampled breath, the double lumen endotrachial tube (ETT) includes a mainendotrachial tube and a second endotrachial tube adapted to samplebreath from a trachea of a subject in an area located in proximity to adistal end of the endotrachial tube (ETT) and a breath sampling lineadapted to connect to the second endotrachial tube of the double lumenendotrachial tube (ETT) through a connector.

The endotrachial tube (ETT) may be a double lumen endotrachial tube(ETT) having main endotrachial tube and a second endotrachial tube,wherein sampling of breath is conducted through the second endotrachialtube. The second endotrachial tube may located essentially inside thelumen of the main endotrachial tube, essentially inside the wall of themain endotrachial tube or partly in both. The second endotrachial tubeis located outside the main endotrachial tube. The second endotrachialtube may have a diameter smaller than the diameter of the mainendotrachial tube.

The second endotrachial tube may include at a proximal end thereof aconnector adapted to connect to a sampling line througb a samplingopening. The connector may further include a suction port adapted toconnect to a fluid suction device and/or to facilitate administration ofmedical agents. The connector may further include a valve, wherein whenthe valve is in a first position flow of sampled breath to the samplingline is allowed and the suction port is blocked and when the valve is ina second position the suction port is opened and flow of sampled breathto the sampling line is blocked.

The second endotrachial tube may include at a distal end thereof two ormore openings adapted to allow flow of breath to the second endotrachialtube.

The double lumen endotrachial tube (ETT) may be adapted for use withchildren, infants and/or neonates.

The double lumen endotrachial tube (ETT) may be adapted for use withsubjects ventilated with High Frequency Ventilation (HFV), such as, butnot limited to, children, infants and/or neonates.

According to some embodiments, the one or more parameters related toconcentration of CO₂ may include Spontaneous End tidal CO₂ (S-EtCO₂),Spontaneous final inspired CO₂ (S-FiCO₂), Continuous (Cont. CO₂),Diffusion CO₂ (DCO₂), density of Spontaneous breathing or any trendthereof or any combination thereof.

According to some embodiments, the endotrachial tube (ETT) may be anuncuffed endotrachial tube (ETT).

According to some embodiments of the invention, there is provided aconnector adapted to connect a second endotrachial tube of a doublelumen endotrachial tube (ETT) to a breath sampling line, the connectorincludes a connecting element adapted to connect to a secondendotrachial tube of a double lumen endotrachial tube (ETT) and asampling opening adapted to connect to a breath sampling line, whereinthe second endotrachial tube is adapted to sample breath, for carbondioxide (CO₂) concentration monitoring, from an area located inproximity to a distal end of the endotrachial tube (ETT).

The connector may further include a suction port adapted to connect to afluid suction device and/or to facilitate administration of medicalagents.

The connector may further include a valve, wherein when the valve is ina first position flow of sampled breath to the sampling line is allowedand the suction port is blocked and when the valve is in a secondposition the suction port is allowed and flow of sampled breath to thesampling line is blocked.

According to some embodiments of the invention, there is provided amethod for evaluating (monitoring) carbon dioxide (CO₂) in breath of asubject, ventilated with High Frequency Ventilation (HFV), the methodincludes sampling breath from a distal area of a trachea of a subjectand evaluating one or more CO₂ related parameters. According to someembodiments, sampling may be conducted through an endotrachial tube(ETT). The endotrachial tube (ETT) may be of any form or shape, forexample, sampling may be conducted through a second endotrachial tube ofa double lumen endotrachial tube (ETT). According to some embodiments,particularly with HFV subjects, distal measurement(s) of CO₂ may beconducted without sampling, but rather by inserting (for example, butnot necessarily, through an ETT) one or more CO₂ sensors to a trachea ofa subject. The one or more CO₂ related parameters may includeSpontaneous End tidal CO₂ (S-EtCO₂), Spontaneous final inspired CO₂(S-FiCO₂) Continuous CO₂ (Cont. CO₂), Diffusion CO₂ (DCO₂), density ofspontaneous breathing or any trend thereof or any combination thereof.

BRIEF DESCRIPTION OF FIGURES

Examples illustrative of embodiments of the invention are describedbelow with reference to figures attached hereto. In the figures,identical structures, elements or parts that appear in more than onefigure are generally labeled with a same numeral in all the figures inwhich they appear. Dimensions of components and features shown in thefigures are generally chosen for convenience and clarity of presentationand are not necessarily shown to scale. The figures (FIGs.) are listedbelow.

FIG. 1 A-C schematically show double lumen Endotrachial Tubes (ETTs),according to some embodiments;

FIG. 2 shows an example of a capnograph display, according to someembodiments;

FIGS. 3 A and B show the linear correlation between distal EtCO₂(dEtCO₂) (A) and proximal EtCO₂ (pEtCO₂) and arterial CO₂ (PaCO₂),according to some embodiments;

FIGS. 4 A and B present the Bland-Altman plots of the differencesbetween distal EtCO₂ (dEtCO₂) (A) and proximal EtCO₂ (pEtCO₂) (B) andarterial CO₂ (PaCO₂), according to some embodiments; and

FIG. 5 shows the linear correlation between distal EtCO₂ (dEtCO₂) andarterial CO₂ (PaCO₂) in subjects ventilated with High FrequencyVentilation (HFV), according to some embodiments.

DETAILED DESCRIPTION OF EMBODIMENTS

In the following description, various aspects of the invention will bedescribed. For the purpose of explanation, specific configurations anddetails are set forth in order to provide it thorough understanding ofthe techniques. However, it will also be apparent to one of skill in theart that the techniques may be practiced without specific details beingpresented herein. Furthermore, well-known features may be omitted orsimplified in order not to obscure the description(s) of the techniques.

According to some embodiments, sampling breath for CO₂ monitoring may beperformed from a position much closer to the bronchial tube (at thelower section of the trachea) than the current sampling position. Thistype of CO₂ sampling and evaluation may also be referred to as a “distalCO₂ measurement”. As discussed hereinabove, the current samplingconfiguration is problematic since it involves sampling from an areaclose to subject's mouth and to the proximal end of the ETT, wherein CO₂is mixed with ventilated air, which eventually leads to erroneous CO₂readings. It was found that sampling breath from a position closer tothe bronchial tube (distal CO₂ measurement) may be less susceptible toair leak and/or mixing of the measured CO₂ with inhaled air. Moreparticularly, sampling breath for distal CO₂ measurement may beperformed at the distal end of the ETT which is adapted to be positionedinside the bronchial tube. According to some embodiments, samplingbreath for distal CO₂ measurement may be performed by inserting acatheter into the ETT, wherein the catheter is adapted to sample CO₂.The catheter may, however, partly occlude or add resistance to theairway. According to some preferred embodiments, sampling breath fordistal CO₂ measurement may be performed through the distal part of whatis known as a double lumen Endotrachial Tube (ETT). Double lumen ETTshave been used so far as a means for suctioning and administration ofsurfactants and similar agents. The second (extra) lumen is typically avery small diameter tube which runs within the wall of the first lumenfrom about halfway down to a point close to the distal exit of the ETT.

Reference is now made to FIG. 1A which schematically shows a doublelumen Endotrachial Tube (ETT), according to some embodiments.Endotrachial Tube (double lumen ETT) 100 includes a main endotrachialtube 102 having a larger diameter and a small diameter tube 104 (forexample, approximately 0.8 mm) located essentially inside and along thewall of main endotrachial tube 102. Small diameter tube 104 has a distalopening 106 a few millimeters before the distal end 108 (towards thesubject's bronchial tube and lungs) of ETT 100. Small diameter tube 104also includes, at its end opposing distal opening 106, a second openinghaving a connector 110, adapted to connect to or allow access to suctiondevices and/or to allow application of agents such as surfactants,medications or the like. According to some embodiments of the inventionadapter 110 may be adapted to connect to a sampling line for samplingCO₂ in exhaled breath from distal end 108 of ETT 100 through smalldiameter tube 104. Proximal opening 130 of main endotrachial tube 102 isadapted to connect to a ventilator.

According to some embodiments, sampling breath for CO₂ monitoring isperformed from the area of the distal end (such as distal end 108) ofthe double lumen EET (such as double lumen ETT 100). The sampling isperformed through the small diameter tube (such as small diameter tube104) of the double lumen ETT.

Tests clearly showed that for subjects with and without High FrequencyVentilation (HFV) (adults, children, infants and/or neonates) distal CO₂measurement performed, for example through a double lumen ETT, produceda significantly better or at least comparable correlation and agreementwith arterial CO₂. For example, better correlation was obtained betweendistal EtCO₂ (dEtCO₂) with arterial CO₂ (PaCO₂) than the correlation ofpEtCO₂ measured by mainstream or sidestream capnograph sampling at thesubject airway proximally with arterial CO₂ (PaCO₂).

Sampling at the distal point of the ETT in subjects and particularly inneonates has another issue: there are many fluids at the distal point.According to some embodiments, in order to solve or reduce the fluidproblem and prevent them from reaching the analyzer, a fluid reducingdevice may be used.

The fluid reducing device may include a standard airway adapter andsampling connector to the sampling line having a stop-cock type valveallowing in its first position to sample breath and in its secondposition to close the sampling line and open an opening for suction offluids from the distal section of the trachea.

According to some embodiments, it may be beneficial if the breathsampling opening of the double lumen is several millimeters inside theendotrachial main tube, with possibly several small apertures (hence, ifone aperture is covered with fluids, the sampling will continue throughone of the remaining openings).

Reference is now made to FIG. 1B which schematically shows a doublelumen Endotrachial tube (ETT), according to some embodiments.Endotrachial Tube (double lumen ETT) 200 includes a main endotrachialtube 202 having a larger diameter and a small diameter tube 204(approximately 0.8 mm) located inside and along the wall of mainendotrachial tube 202. Small diameter tube 204 has a distal opening 206a few millimeters before the distal end 208 (towards the subject'sbronchial tube and lungs) of ETT 200. Distal opening 206 of smalldiameter tube 204 has several (in this case three) additional apertures209. When one or more of apertures 209 is blocked with fluids, thesampling will continue through one or more of the remaining openings.

Small diameter tube 204 also includes, at its end opposing distalopening 206, a second opening having a connector 210. Connector 210includes a connecting dement 211 adapted to connect to small diametertube 204. Connector 210 further includes a sampling opening 212 adaptedto connect to a sampling line 214, optionally with drying tube 216adapted to absorb and/or pervaporate fluids present in the sampledbreath. Connector 210 also includes suction port 218 through whichsuction of fluids from the distal section of the trachea can beperformed. Suction port 218 may also be adapted to allow application ofagents such as surfactants, medications or the like. Connector 210further includes valve 220. Valve 220 has two optional positions, afirst position (as shown in FIG. 1B) allows the flow of air sampledthrough small diameter tube 204 to drying tube 216 and sampling line 214and on to the analyzer (such as a capnograph). The second position (notshown) of valve 220 approximately perpendicular to the first position.In the second position, valve 220 blocks the flow of air sampled throughsmall diameter tube 204 to drying tube 216 and sampling line 214 andallow the flow towards suction port 218. Valve 220 (or any other valve)may be adjusted by a user to allow sampling and from time to time, asneeded or every period of time, allow suction or application ofmedication while blocking the sampling path. Proximal opening 230 ofmain endotrachial tube 202 is adapted to connect to a ventilator. Valve220 (or any other valve) may also be automatically adjusted by acontroller to allow sampling and every period of time trigger suction orapplication of medication while blocking the sampling path. Thecontroller may also be adapted to stop the sampling pump upon blockingthe sampling line.

According to embodiments of the invention, the connector (such asconnector 210) may be integrally formed with the second endotrachialtube, which may also be referred to as small diameter endotrachial tube(such as small diameter tube 204), or may be adapted to be (removably orpermanently) affixed or mounted on the proximal end of the secondendotrachial tube.

According to some embodiments, sampling breath for CO₂ monitoring isperformed from the area of the distal end (such as distal end 208) ofthe double lumen EET (such as double lumen ETT 200). The sampling isperformed through the small diameter tube (such as small diameter tube204) of the double lumen ETT.

For clarification and the avoidance of doubt, a “double lumen ETT” or“double lumen endotrachial tube” includes an endotrachial tube with twoor more lumens. The two or more lumens may have the same or differentinternal diameters.

The fluid reducing device may also include a drying tube, such as butnot limited to a Nafion® tube or any other drying tube. In case ofstandard ventilation (where the waveform is analyzed) particularly ininfants and neonates, it should be noted that using standard largerwater traps, collectors, filters or the like may add extra dead space orminor interference to the breath flow which may effect the waveform.

In case of HFV it may be possible to add filter(s), liquid trap(s),dryer tubes or the like, since in HFV mode response time less criticalcompared to standard ventilation, though its (their) size may dampensomewhat the spontaneous breaths.

According to some embodiments, one or more of the small diameter tubesof double-lumen ETTs (such as small diameter tubes 104 and 204) may beused for insertion of a sensor or a detector adapted to reachapproximately the distal section of the trachea and sense (detect)breath elements such as CO₂. This may replace sampling or conducted inaddition to sampling. Such sensor can be a chemical sensor, electronicsensor, optic sensor or any other sensor/detector. For example, thesmall diameter tubes of a double-lumen ETT may be adapted to receive afiber optics adapted to transmit and return radiation (for example IRradiation at a wavelength that CO₂ absorbs), and thus detect one or morebreath parameters (such as CO₂ levels or waveforms in case of standardventilation). In another embodiment, radiation (such as light) may beemitted through the main endotrachial tube (such as main endotrachialtubes 102 and 202) in such way that light entered through the mainendotrachial tube is reflected by an appropriate reflector back throughan optical fiber in the small diameter tube back to an appropriatedetector.

According to some embodiments, there is also provided an ETT, having amain endotrachial tube and a second endotrachial tube (optionally havinga smaller diameter than the main endotrachial tube). The secondendotrachial tube is located outside the main endotrachial tube (asapposed to inside of the main endotrachial tube as shown above). Thedistal opening of the second endotrachial tube may be in proximity tothe distal opening of the main endotrachial tube but may also beshorter, such that upon insertion to the trachea, it only would onlyreach the cavity of the mouth for sampling exhaled air that escapedaround the uncuffed ETT. This second line may also (as above) connect bya stop-cock to the main (neonatal) sampling adapter. A user could togglebetween the two sampling points.

According to some embodiments, the main endotrachial tube may include,at or in proximity to its distal end, a mechanism that is adapted toopen when positive pressure from a ventilator pushes in the air forventilation, while close on exhalation. This way, the exhaled breathwill be forced to return around the outside of the main endotrachialtube to be collected by the second endotrachial tube. It is notedhowever, that a mechanism such as mechanism 340 may apply to standardventilation, while, in HFV where the main concept is base on diffusion,such mechanism may not be applicable.

Reference is now made to FIG. 1C which schematically shows a doublelumen Endotrachial tube (ETT), according to some embodiments.Endotrachial Tube (double lumen ETT) 300 includes a main endotrachialtube 302 and a second endotrachial tube 304 located outside and alongthe wall of main endotrachial tube 302. Second endotrachial tube 304 hasa distal opening 306 at approximately one third of the way of mainendotrachial tube 302, so that upon insertion to the trachea, it onlywould only reach the cavity of the mouth for sampling exhaled air thatescaped around uncuffed ETT 300.

Second endotrachial tube 304 also includes, at its end opposing distalopening 306, a second opening having a connector 310. Connector 310includes a sampling opening 312 adapted to connect to a sampling line314. Connector 310 also includes suction port 318 through which suctionof fluids from the distal section of the trachea can be performed.Suction port 318 may also be adapted to allow application of agents suchas surfactants, medications or the like. Connector 310 further includesvalve 320. Valve 320 has two optional positions, a first position (asshown in FIG. 1C) allows the flow of air sampled through small diametertube 304 to sampling line 314 and on to the analyzer (such as acapnograph). The second position (not shown) of valve 320 approximatelyperpendicular to the first position. In the second position, valve 320blocks the flow of air sampled through small diameter tube 304 tosampling line 314 and allow the flow towards suction port 318. Valve 320(or any other valve) may be adjusted by a user to allow sampling andfrom time to time, as needed or every period of time, allow suction orapplication of medication while blocking the sampling path. Proximalopening 330 of main endotrachial tube 302 is adapted to connect to aventilator. Valve 320 (or any other valve) may also be automaticallyadjusted by a controller to allow sampling and every period of timetrigger suction or application of medication while blocking the samplingpath. The controller may also be adapted to stop the sampling pump uponblocking the sampling line.

Main endotrachial tube 302 also includes, in proximity to its distal end308, a mechanism 340 that is adapted to open when positive pressure froma ventilator pushes in the air for ventilation, while close onexhalation. It is noted however, that a mechanism such as mechanism 340may apply to standard ventilation, while, in HFV where the main conceptis base on diffusion, such mechanism may not be applicable. This way,the exhaled breath will be forced to return around the outside of themain endotrachial tube to be collected by the second endotrachial tube.

According to some embodiment, a miniature nano-technology CO₂ sensor maybe placed in the trachea through the small diameter tube of the doublelumen ETT. This configuration may show measuring the CO₂ in-situ.According to other embodiments, the CO₂ nano sensor can also be placedin any ETT not necessarily double lumen ET. Similarly, any other sensor,such as an O₂ sensor may also be placed in (and/or through) the smalldiameter tube of the double lumen ETT or any ETT in addition or insteadof the CO₂ nano sensor. According to some embodiments, the sensor may bedisposable.

High Frequency Ventilation (HFV)

Additional or alternative embodiments of the invention are generallydirected to a method and apparatus for using capnography in monitoringbreath carbon dioxide (CO₂) in subjects, particularly, but not limitedto, small children and infants, who are ventilated by High FrequencyVentilation (HFV) technique.

As discussed above when considering capnography for replacing at leastsome of the blood gas samples, and in general to provide continuousmonitoring for HFV (such as HFOV) mode of ventilation, some difficultiesarise. These difficulties include very high ventilation frequencies,lack of “clear”, “textbook” breath cycle and when sampling at thestandard position for capnography, either in mainstream or sidestream,the CO₂ concentration is much lower than what is really occurring in thelungs.

According to some embodiments of the invention, there are provided amethod and apparatus for CO₂ sampling and monitoring in subjects (forexample, but not limited to, children, infants, and neonates) ventilatedby the HFV mode while overcome issues related to difficulties such asthose discussed herein.

According to some embodiments of the invention, since in HFV one canexpect long periods without observing typical waveforms and breathcycles, which are not the result of apnea, the platform for CO₂ samplingin HFV subjects should take this into account or be insensitive to suchinstances.

New Parameters to be Provided to the User

This following describes, according to some embodiments of theinvention, possible requirements, improvements and/or changes needed inorder to provide an appropriate Capnography mode of operation withsubjects ventilated with HFV.

According to some embodiments, there are provided new parameters fordefining HFV mode. These parameters may optionally have their own alarmmanagement and trend characteristics. Of course, the names given tothese parameters are not binding and are only optional.

According to some embodiments, the following parameters may be definedand used for capnography in subjects ventilated with HFV. Some of theseparameters may be used instead of or in addition to standard respiratoryrate (RR) EtCO₂ parameters or other known standards.

a) Cont. CO₂—Continuous CO₂: According to some embodiments, this is amain value used in HFV capnography and can be calculated as the averageCO₂ reading (concentration) over the last “x” seconds (which could be 5seconds or 1 to 60 seconds or any other period), updated every “y”second (“y” could be 1 to 60 seconds, or any other period). If withinthis period a spontaneous breath is detected or even the possiblebeginning of such a breath is suspected (to be defined in section “e”below), then the last Cont. CO₂ value could be frozen until a new period(such as, a 5-second period) has passed without any identifiedspontaneous breath. If the spontaneous breaths continue for more thanpossibly “z” seconds (such as, 60 seconds) without a “w” second (forexample, 5 second) gap, the Cont. CO₂ value may be determined andoptionally displayed as invalid (for example a dash is provided in placeof the value).

b) S-EtCO₂—Spontaneous EtCO₂: If a spontaneous breath cycle (to bedefined in section “e” below) is recognized (typically a result ofspontaneous breathing), then, according to some embodiments, the highestCO₂ (concentration) value of the breath, S-EtCO₂ (Spontaneous EtCO₂),may be measures and optionally displayed. The displayed value may be thehighest result that was collected over the last “m” seconds (possibly 1to 60 seconds). Again, it may be updated every period of time (once asecond for example). If for “n” seconds (for example, 20 seconds) thereis no new breath, the S-EtCO₂ value may be determined and optionallydisplayed as invalid (for example a dash is provided in place of thevalue).

c) S-FiCO₂—Spontaneous fractional concentration of final inspired CO₂:If a breath cycle is recognized, then, according to some embodiments,the lowest CO₂ (concentration) value in the breath cycle (Spontaneousfractional concentration of final inspired CO₂ S-FiCO₂) may be used andthe value obtained and optionally displayed being the lowest collectedover the last “u” seconds (possibly 1 to 60 seconds). Again, it may beupdated every period of time (once a second for example). If for “t”seconds (for example, 20 seconds) there is no new breath, the S-EtCO₂value may be determined and optionally displayed as invalid (for examplea dash is provided in place of the value).

d) DCO₂—Diffusion (gas transport coefficient) CO₂, DCO₂: This parametermay be similar to the conventional ventilation parameter that is theproduct of tidal volume and frequency, known as minute ventilation,which aptly describes pulmonary gas exchange. The gas transportcoefficient which defines the CO₂ elimination correlates to the productof “oscillatory volume” squared and the frequency. For this purpose, itwould be necessary to enable entering of the HFV ventilator parametersinto the Capnograph.

e) Inst. CO₂—Instantaneous CO₂: a raw unprocessed measurement of CO₂.According to some embodiments, every period of time (for example, onceevery 50 msec, a CO₂ measurement is performed). If the measured CO₂change of at least “c” mmHg (“c” can for example be between 1 and 10mmHg) above (or below) the Cont. CO₂ current (latest) value and lastingfor at least “k” milliseconds, msec (for example, 200 msec), aspontaneous breath is suspected. The system may trace for a peak to peak(PTP) of “c” mmHg lasting more than a minimal “k” period, for example200 msec. During this stage the Cont. CO₂ value may be frozen as statedabove. In case of a timeout (of for example, 3 seconds) with no “c” mmHgPTP, the PTP trace may be stopped and the Cont. CO₂ calculation may beresumed. A spontaneous breath is counted every 2 consecutive occurrencesof “c” mmHg PTP.

f) “Low CO₂”: Since in HFV one can expect long periods without observinga typical waveforms and breath cycles, there is no meaning to the term“apnea” or “no breath”, hence the term “low CO₂” may be used instead.

g) High and low Cont. CO₂ alarms: According to some embodiments, thealarms relating to RR, high and low EtCO₂ may be disabled and Cont. CO₂high and low may be enabled.

h) Density of spontaneous breaths: According to some embodiments theDensity of spontaneous breaths may be calculated. Thus value may beobtained by calculating when percentage of the time the subject isspontaneously breathing.

i) According to some embodiments, trends of any CO₂ related parameter(such as Cont. CO₂ may be provided and optionally presented as a graphor table that demonstrates the change of the parameter over time.

j) According to some embodiments, the Cont. CO₂ value may be displayedat a position where in normal mode (non-HFV) the EtCO₂ value isdisplayed. The other two parameters (S-EtCO₂ and FiCO₂ ) may bedisplayed where in normal mode (no-HFV) the RR and FiCO₂ are displayed.

k) According to some embodiments, the display may include two parts:

-   -   1) A main waveform display having a sweep rate, which is slower        than the standard ventilation (non-HFV) generally in the range        of 0.1 to 10 mm/second. This mode displays the Continuous (Cont.        CO₂) with the sporadic spontaneous breaths superimposed on it.        An example of a main waveform display can be seen in the top        graph of FIG. 2, which shows an example of a capnograph display        of a subject ventilated by HFV, according to some embodiments.        The top graph shows the values of Cont. CO₂ in mmHg over time        (seconds, sec). The sections of the graph having clear “dips”        indicate spontaneous breathing.    -   2) A display having a slower sweep rate than that of the main        waveform display (section 1 hereinabove), for example in the        range of 0.1 to 10 mm/min. This slower display shows the trend        of the Continuous (Cont. CO₂), or in other words, how the Cont.        CO₂ is changing over a period of time (for example, 90 min).        This type of data may reduce or even eliminate the use of blood        gas, since, for example, just by looking at it the doctor may        know if the CO₂ level is improving since the last blood gas test        obtained from the subject. An example of such a trend display        can be seen in the bottom graph of FIG. 2, which shows the trend        of Cont. CO₂ in mmHg over time (minutes, min). In addition to        these graphs, values of Cont. CO2, S-EtCO₂, S-FiCO₂ as well as        SpO2 and PR (pulse oximetery) may also be presented.

l) According so some embodiments, there is provided a means for manually(or automatically) entering an event mark, for example, defining a bloodgas. A red spot, for example, or similar (possibly a sigh, a letter or acombination of letters such as “b.g.”) may be placed on the slower trenddisplay so that the doctor can easily see trends of CO₂ relative to thelast blood gas time. It is preferred that one could also add the valuesof the blood gas in any form (values, graphical etc.) so that they canbe displayed on the trend with the sampled CO₂ values.

According to some embodiment of the invention, the term “distal” or“distal end” may refer to a position located (or adapted to be located)towards a subject's lungs.

According to some embodiment of the invention, the term “proximal” or“proximal end” may refer to a position located (or adapted to belocated) towards a subject's mouth.

According to some embodiment of the invention, the term “mainendotrachial tube” may refer to a part of an endotrachial tube throughwhich ventilation may be performed.

According to some embodiment of the invention, the term “secondendotrachial tube” may refer to a part of an endotrachial tube which isnot directly used for ventilation. A second endotrachial tube may besmaller in diameter than the main endotrachial tube. A secondendotrachial tube may be integrally formed with the main endotrachialtube or connected thereto.

According to some embodiment of the invention, the term “sampling line”or “breath sampling line” may refer to any type of tubing(s) or any partof tubing system adapted to allow the flow of sampled breath, forexample, to an analyzer, such as a capnograph. The sampling line mayinclude tubes of various diameters, adaptors, connectors, valves, dryingelements (such as filters, traps, trying tubes, such as Nafion® and thelike).

EXAMPLES Example 1 Correlation between Sampling through a Double LumenETT and Blood Gas Study Design

A prospective observational study was conducted at Bnai-Zion MedicalCenter, Haifa, Israel. Infants were connected simultaneously to proximaland distal EtCO₂ monitors, and the measurements were compared to PaCO₂drawn for patient care. Measurements of distal EtCO₂ (dEtCO₂) were notused for patients' clinical care. The study was approved by theinstitutional review board. All the parents signed an informed consentprior to participating in the study.

The primary outcome measure was to evaluate the accuracy and thecorrelation of Microstream dEtCO₂ with the gold standard of PaCO₂. Thesecondary outcome measure was to compare these findings to the morestandard and commonly used method of mainstream pEtCO₂.

Study Population

Included in the study were all intubated infants in the NICU during thestudy period, who had the doable lumen endotrachial tubes (ETT) and thattheir parents signed an informed consent. Excluded were infants with asingle lumen endotrachial tube.

All infants who needed an ETT were intubated in the delivery room or inthe NICU by a double lumen tube (Uncuffed Tracheal Tube, MallinckrodtInc., Chih, Mexico). This ETT has an extra small lumen foradministration of exogenous surfactant or for measurements of distalpressures close to the carina. In this study this side port was used tomeasure dEtCO₂ only.

Intubated infants were monitored by the two capnograms simultaneously.The side-stream dETCO₂ was measured distally by a Microstream capnographvia a Microstream cannula (Oridion Medical Inc., Needham, Mass.). Themain-stream pETCO₂ was measured via capnogram connected to the proximalend of the ETT (Philips IntelliVue patient monitor, CapnographyExtension M3014A, Philips, Boeblingen, Germany). Readings from the twomethods were charted at the time of blood sampling for routine patientcare via an indwelling arterial line, and compared to PaCO₂ level (OmniAVL, Roche Diagnostic Gmbh, Graz, Austria). Before each blood samplingit was assured that an adequate reading of pEtCO₂ and a reliablewaveform on the Microstream capnograph (continuous steady waveform ofaspired CO₂ throughout the ventilatory cycle), and cleared secretionsfrom the side port of the ETT for dEtCO₂ measurement, (by inserting 5 mlof air). Microstream cannulas blocked by secretions were replaced asneeded.

Data on the patients' characteristics, type of their pulmonary orcardiac disease and the severity of pulmonary disease (by oxygenationindex defined as fractional inspired of oxygen [FiO₂]×mean airwaypressure/PaO₂ and by the level of ventilation perfusion mismatchassessed by PaO₂/PAO₂ ratio) was collected. Severe lung disease wasdefined as: PaO₂/PAO₂ ratio<0.3 (18, 19) or OI>10; mild-moderate lungdisease: PaO₂/PAO₂ ratio>0.3 and OI<10 (PAO₂ was calculated by:FiO₂×[Barometric pressure-47]−PaCO₂/0.8], PaCO₂ was assumed the same asalveolar PACO₂.

A bias ≦5 mmHg was considered a low bias and >5 mmHg a high bias (9,10).

The consistency of EtCO₂ monitoring (proximal and distal) within eachpatient was assessed by examining the relationship between the change inPaCO₂ and the change EtCO₂ in consecutive samples.

Statistical Analysis

The correlation of distal and proximal EtCO₂ and PaCO₂ was evaluated bylinear regression analysis and assessed the agreement between thesemeasurements (bias [mean difference] and precision [standard deviationof the differences]) by the Bland-Altman technique (22).

The correlation between the changes in PaCO₂ and the simultaneouschanges in proximal and distal EtCO₂ were evaluated for consecutivemeasurements within each patient by linear regression analysts.

Level of significance was set at p<0.05. SigmaStat version 2.03,Chicago, Ill. and the Minitab version 12.23, State College, Pa.statistical softwares were employed.

Results

Twenty-seven infants participated in the study and 222 measurements ofdistal EtCO₂ and 212 of proximal EtCO₂ were analyzed. In 10 infantsproximal EtCO₂ could not be measured continuously. Table 1 shows thecharacteristics of the patients who participated in the study.

TABLE 1 Patients characteristics (n = 27) Median Range Gestational age(weeks) 32.5 (24.8-40.8) Birth weight (g) 1835  (490-4790) Age ofenrolment (days) 1  (1-26) Number of observations 8  (1-24) pH 7.346.5-7.5 FiO₂* 0.31 0.21-1.00 PaO₂/PAO₂ ratio* 0.50 0.06-2.38 Oxygenationindex (OI)*** 3.29 0.63-23.0 Primary diagnosis (n = 27 infants)Respiratory distress syndrome 19 Tracheo-esophageal fistula andesophageal astresia  3 Pneumonia  1 Primary pulmonary hypertension  1Meconium aspiration syndrome  1 Hypoxic ischemic encephalopathy  1Necrotizing enterocolitis  1 *FiO₂ Inspired oxygen fraction; **PaO₂/PAO₂alveolar/arterial oxygen tension ratio; ***OI = FiO₂ X mean airwaypressure/PaO₂

The median (range) levels of PaCO₂, dEtCO₂, pEtCO₂ were 46.3 (24.5-99.7)mmHg, 46.0 (20.0-98.0) mmHg, and 37.0 (12.0-71.0) mmHg, respectively.

FIGS. 3 A and B show the linear correlation between distal EtCO₂, dEtCO₂(A) and proximal EtCO₂, pEtCO₂ (B) with arterial PCO₂, according to someembodiments. While the correlation coefficient (r) of dEtCO₂ and PaCO₂was adequate (r=0.72, p<0.001), the r of the pEtCO₂ was poor (r=0.21,p=0.002).

FIGS. 4 A and B present the Bland-Altman plots of the differencesbetween distal EtCO₂, dEtCO₂ (A) and proximal EtCO₂, pEtCO₂ (B) andarterial CO₂, PaCO₂, according to some embodiments. The mean difference(bias) and the standard deviation of the differences (precision) for thedEtCO₂ were −1.5±8.7 mmHg, and for the pEtCO₂ −10.2±13.7 mmHg,respectively. The correlating medians (25 and 75 percentiles) were: −1.1(−5.6 and 2.7) and −10.3 (−16.0 and −0.8), respectively. Although both,distal and proximal EtCO₂ levels underestimated the PaCO₂ level, dEtCO₂was more accurate titan pEtCO₂ as a non-invasive measure of PaCO₂.

dEtCO₂ (21 samples) remained reliable as a measure of PaCO₂, whilepEtCO₂ (19 samples) was distorted on the high range of PaCO₂ levels (≧60mmHg) (r=0.77, p<0.001 and r=0.21, p=0.38; bias±precision: −4.8±7.9 and−33.3±20.0; respectively).

Table 2 shows the effect of the severity of pulmonary disease (assessedby PaO₂/PAO₂ ratio or by OI) on the accuracy of distal and proximalEtCO₂ readings. It was found that dETCO₂ still correlated with PaCO₂,but its bias increased with the severity of pulmonary disease.

TABLE 2 Relation between EtCO₂ values and severity of lung disease Mildto Moderate Severe lung disease Mean (SD); r, p value Mean (SD); r, pvalue PaO₂/PAO₂ ratio >0.3 (n = 168) ≦0.3 (n = 63) P (Et-a distal) CO₂−0.24 ± 7.3; 0.74,  −4.2 ± 10.5; 0.64, <0.001 <0.001 P (Et-a proximal)CO₂  −9.1 ± 14.0; 0.07, −12.5 ± 12.5; 0.35, =0.34 <0.01 Oxygenationindex <10 (n = 216) ≧10 (n − 16) P (Et-a distal) CO₂  −0.7 ± 8.2; 0.69, −9.0 ± 8.1; 0.77, <0.001 <0.001 P (Et-a proximal) CO₂  −9.8 ± 13.9;0.13, −13.0 ± 9.8; 0.52, =0.07 =0.054All CO₂ Levels in mmHg

The changes in PaCO₂ and the simultaneous changes in proximal and distalEtCO₂ were evaluated for consecutive measurements within each patient.The mean changes in PaCO₂ were 0.12±9.3 mmHg and in dEtCO₂ 0.90±10.8mmHg, with r between the changes of 0.49, p<0.001. Mean change in pEtCO₂was −0.02±8.5 mmHg, with r of 0.17, p<0.05, compared to the simultaneouschanges in PaCO₂.

This study shows that the novel method of measuring dEtCO₂ through adouble-lumen ETT had a better correlation and agreement with PaCO₂ whencompared to the standard mainstream pEtCO₂ method in neonates. Theaccuracy of dEtCO₂ decreased but it remained a reliable measure of PaCO₂even in the high range of PaCO₂ (≧60 mmHg) or in condition of severelung disease.

It was found that dEtCO₂ was an accurate and reliable non-invasivemethod for estimating PaCO₂. It had a good correlation with PaCO₂(n=222, r=0.72, p<0.001), which was slightly lower compared tomainstream pEtCO₂ (n=411, r=0.83, p<0.001) as previously reported forNICU infants by Rozycki et al (10). The bias reported for dEtCO₂(−1.5±8.7 mmHg) was even smaller than that reported by Rozycki et al formainstream pEtCO₂ (−6.9±6.9 mmHg), and was well <5 mmHg, which isconsidered within the good agreement range (9, 10). In the study, thecorrelation and the agreement of dEtCO₂ with PaCO₂ were better thanthose for mainstream pEtCO₂. Several investigators reported similarresults for distal and proximal sidestream EtCO₂ (17, 18) while othersreported comparable accuracy of distal and proximal mainstream EtCO₂(11). However, neither of these studies measured dEtCO₂ by a doublelumen ETT, nor did they use the Microstream technique. The study resultsregarding the mainstream pEtCO₂ should be interpreted with caution, asothers reported better results for that method (10). This could resultfrom different conditions in the different studies reflected by mixtureof patients, severity of their lung disease, levels of leak around theETT, and instrumentation used for measurements.

Severity of disease was reported to affect the accuracy of capnometry inseveral studies. The more severe the ventilation perfusion mismatch, thehigher the difference between EtCO₂ and PaCO₂ (9, 20). Parenchymal lungdisease with ventilation perfusion mismatching is a common feature inNICUs. Sivan et al (20) reported that PaO₂/PAO₂ ratio>0.3 was associatedwith better agreement between EtCO₂ and PaCO₂ and Hagerty et al (9)found a higher gradient between EtCO₂ and PaCO₂ when comparing newbornwith pulmonary disease and those receiving mechanical ventilation fornon-pulmonary conditions. Different results were reported by otherinvestigators. Tingay et al (19) found that the EtCO₂ bias wasindependent of severity of lung disease and Rozycki et al (10) reportedthat measures of degree of lung disease (ventilation index andoxygenation index) had small influence on the degree of bias. In thestudy the agreement of dEtCO₂ and PaCO₂ decreased, but the bias inpatients with PaO₂/PAO₂ ratio<0.3 remained <5 mmHg. It was assessedwhether the level of PaCO₂ affected the accuracy of EtCO₂ readings, andfound it to affect the pEtCO₂ much more than the dEtCO₂, which remainedwith adequate agreement with the PaCO₂. Rosycki et al did not find thatthe accuracy of pEtCO₂ was affected by the PaCO₂ level (10). Thefindings suggest that dEtCO₂ as evaluated in the study could be used asa reliable non-invasive method for PaCO₂ assessment in the full spectrumof NICU patients.

Although the Microstream sidestream capnography was used previously in(only) two studies in newborns (9, 19), this is the first time a doublelumen ETT is used for the disclosed purpose, which allowed continuousmeasurement of dEtCO₂ via its extra lumen.

The intention of the Microstream technique is to improve the accuracy ofsidestream capnometry which is traditionally considered less accuratethan the mainstream capnometry (11, 13, 14, 15, 16). Microstreamcapnography employs a sampling flow rate of 50 ml/min, approximately onethird of that used by previous studies with conventional sidestreamsystems. This low flow rate eliminates the competition for tidal volumeand also decreases condensation within the system. Because of the highlyCO₂-specific infrared source (emission that exactly matches theabsorption spectrum of the CO₂ molecule), the sample cell utilizes amuch smaller volume (15 μl) that permits a low flow rate withoutcompromising response rate or accuracy. These features preserve accuracyby preventing mixing of the small inspiratory and expiratory volumesobserved in newborns, while rapid response time is maintained by laminargas flow throughout the breathing circuit (22). The new low-flowsidestream capnograph (Oridian Medical Inc., Needham, Mass., USA) wastested when connected to the side port of the proximal ETT by Hagerty etal (9), and they reported a gradient of 3.4±2.4 mmHg in ventilatedinfant without pulmonary disease and 7.4±3.3 in those with pulmonarydisease. Tingay et al also used the Microstream technique (AgilentMicrostream system, Andover, Mass., USA) for monitoring pEtCO₂ ininfants during neonatal transport. They reported that the pEtCO₂ had alinear relation with PaCO₂ but had an unacceptable underestimation ofPaCO₂ (8.2±5.2 mmHg), and did not trend reliably over time within anindividual patient. In the study, using the Microstream technique(Oridion Medical Inc., Needham, Mass., USA), but measuring dEtCO₂ viathe side port of the double lumen ETT, the agreement with PaCO₂ improvedin infants with both mild and severe pulmonary disease (−0.24±7.3, and−4.2±10.5; respectively). The improvement could be related to distalmeasurements of EtCO₂. This technique which measures EtCO₂ close to thecarina, may be less affected by the ventilatory circuit flow and leaksaround the uncuffed ETTs used in neonates and thus better represent theaccurate PaCO₂. dEtCO₂ as opposed to pEtCO₂ are not affected by flowsensors which are commonly used nowadays with the new ventilators (flowsensors in the study prevented the use of pEtCO₂ in few infants becauseof inadequate continuous measurements).

The novel method of measuring dEtCO₂ via a double-lumen endotrachialtube was found to have good correlation and agreement with PaCO₂, and isthus a reliable in conditions of severe lung disease dEtCO₂ was moreaccurate than the standard mainstream pEtCO₂ method as assessed in thestudy. EtCO₂ does not replace PaCO₂, but may be useful for trending andfor real time continuous screening of abnormal PaCO₂ levels. Asnoninvasive CO₂ monitoring may be of importance for the short and longterm outcome of intubated neonates, and as the current available methodsare limited, medical teams should consider the use of this non-invasivemethod of assessing PaCO₂ in NICUs.

Example 2 Correlation between Sampling through a Double Lumen ETT andBlood Gas in Patients Ventilated by HFV

Eight patients ventilated by HFV were tested, comparing mainstreamcapnography to Microstream capnography wherein the sampling line isconnected to the distal end of a double lumen ETT. In most of the cases2.5 mm ETT (internal diameter of the main endotrachial tube) were used.Correlation to blood gas was used as the reference.

Continuous distal sampling with minor liquid issues was conducted(without having to toggle). Further, two Nafion® pieces were placedalong the sampling line, one next to the double lumen connector, and oneabout 40 cm down the line. The second Nafion® was used since often theneonate is in a controlled humidified incubator, and hence one Nafion®must be placed also in the outside environment. The results aredescribed in FIG. 5 which shows the linear correlation between distalEtCO₂, dEtCO₂ and arterial CO₂, PaCO₂ in patients ventilated with HighFrequency Ventilation (HFV), according to some embodiments. Thecorrelation between dEtCO₂ and PaCO₂ was shown to be much better thanthe correlation between pEtCO₂ and PaCO₂.

In the description and claims of the application, each of the words,“comprise” “include” and “have”, and forms thereof, are not necessarilylimited to members in a list with which the words may be associated.

The invention has been described using various detailed descriptions ofembodiments thereof that are provided by way of example and are notintended to limit the scope of the invention. The described embodimentsmay comprise different features, not all of which are required in allembodiments of the invention. Some embodiments of the invention utilizeonly some of the features or possible combinations of the features.Variations of embodiments of the invention that are described andembodiments of the invention comprising different combinations offeatures noted in the described embodiments will occur to persons withskill in the art. It is intended that the scope of the invention belimited only by the claims and that the claims be interpreted to includeall such variations and combinations.

REFERENCES, INCLUDED HEREIN BY REFERENCE IN THEIR ENTIRETY

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What is claimed is:
 1. A method for evaluating concentration of carbondioxide (CO₂) in a subject's breath, the method comprising: inserting anendotrachial tube (ETT) to a subject in a need thereof; sampling breathfrom an area in the trachea located in proximity to a distal end of theendotrachial tube (ETT); and evaluating one or more parameters relatedto concentration of CO₂ in the sampled breath.
 2. The method of claim 1,wherein sampling breath comprises inserting a second tube into theendotrachial tube (ETT), such that the second tube reaches the arealocated in proximity to the distal end of the endotrachial tube (ETT),and sampling the breath through the second tube.
 3. The method of claim1, wherein the endotrachial tube (ETT) is a double lumen endotrachialtube (ETT) having a main endotrachial tube and a second endotrachialtube, wherein sampling of breath is conducted through the secondendotrachial tube.
 4. The method of claim 3, wherein the secondendotrachial tube is located essentially inside the lumen of the mainendotrachial tube, essentially inside the wall of the main endotrachialtube or partly in both.
 5. The method of claim 3, wherein the secondendotrachial tube is located outside the main endotrachial tube.
 6. Themethod of claim 3, wherein the second endotrachial tube has a diametersmaller than the diameter of the main endotrachial tube.
 7. The methodof claim 3, wherein sampling further comprises connecting a samplingline to a connector located at a proximal end of the second endotrachialtube.
 8. The method of claim 3, further comprising performing suction offluid from the second endotrachial tube, wherein when suction isperformed sampling is temporarily stopped and when sampling is performedsuction is stopped.
 9. The method of claim 1, for use with children,infants and/or neonates.
 10. The method of claim 1, for use withsubjects ventilated with High Frequency Ventilation (HFV).
 11. Themethod of claim 10, wherein the one or more parameters related toconcentration of CO₂ comprise Spontaneous End tidal CO₂ (S-EtCO₂),Spontaneous final inspired CO₂ (S-FiCO₂), Continuous (Cont. CO₂),Diffusion CO₂ (DCO₂), density of Spontaneous breathing or any trendthereof or any combination thereof.
 12. The method of claim 1, whereinthe endotrachial tube (ETT) is an uncuffed endotrachial tube (ETT). 13.A double lumen endotrachial tube (ETT) adapted for sampling breath froma subject for the evaluation of one or more parameters related toconcentration of carbon dioxide (CO₂) in the sampled breath, the doublelumen endotrachial tube (ETT) comprising: a main endotrachial tube; anda second endotrachial tube adapted to sample breath from a distalposition in a trachea of a subject.
 14. The double lumen endotrachialtube (ETT) of claim 13, wherein the second endotrachial tube is locatedessentially inside the lumen of the main endotrachial tube, essentiallyinside the wall of the main endotrachial tube or partly in both.
 15. Thedouble lumen endotrachial tube (ETT) of claim 13, wherein the secondendotrachial tube is located outside the main endotrachial tube.
 16. Thedouble lumen endotrachial tube (ETT) of claim 13, wherein the secondendotrachial tube has a diameter smaller than the diameter of the mainendotrachial tube.
 17. The double lumen endotrachial tube (ETT) of claim13, wherein the second endotrachial tube comprises at a proximal endthereof a connector adapted to connect to a sampling line through asampling opening.
 18. The double lumen endotrachial tube (ETT) of claim17, wherein the connector further comprises a suction port adapted toconnect to a fluid suction device and/or to facilitate administration ofmedical agents.
 19. The double lumen endotrachial tube (ETT) of claim18, wherein the connector further comprises a valve, wherein when thevalve is in a first position flow of sampled breath to the sampling lineis allowed and the suction port is blocked and when the valve is in asecond position the suction port is opened and flow of sampled breath tothe sampling line is blocked.
 20. The double lumen endotrachial tube(ETT) of claim 13, wherein the second endotrachial tube comprises at adistal end thereof two or more openings adapted to allow flow of breathto the second endotrachial tube.